Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Early intervention with enzyme replacement therapy (ERT) with intravenous infusions of recombinant human alpha-galactosidase A consistently and clearly decreases Gb3 levels in the blood plasma and clears vascular endothelial cellular lysosomal inclusions. While effects on other tissue are no so obvious, ERT, when initiated early, seems to prevent cellular damage and disease complications.
[43] Certain genetic defects can make enzyme replacement treatment less effective or totally ineffective and can lead to renal failure.
[44]

Lidove et al
[45] noted that 2 formulations of the enzyme alpha-galactosidase A are used in Europe: agalsidase alpha (produced in a human cell line) and agalsidase beta (produced in Chinese hamster ovary cells). Two different enzyme preparations are made by different companies: agalsidase alpha (Replagal, Shire) and agalsidase beta (Fabrazyme, Genzyme). Lin et al found that patients can be switched form alpha-galactosidase to agalsidase beta with no ill effect after one year follow-up.
[46]

Lidove et al,
[45] based on a review of 11 trials, reported that these preparations both appear to have clinical efficacy but that further assessments are needed. The trials have not been optimal in design and would benefit from a prospective design and a specific investigation into the effects of ERT in women and on the use of ERT early in the course of Fabry disease to halt organ damage before it starts. Additionally, Kim et al
[47] noted that the pulmonary manifestations of Fabry disease respond positively to ERT.

A report from France in 2012
[48] studied the use of miglustat hydrochloride, an investigational pharmacological chaperone, given orally at 150 mg every other day in 2 phase 2 studies. Researchers found miglustat hydrochloride increased α-Gal A activity of at the very least 50% in blood, skin, and kidney in 6 of 9 patients. In this study, α-Gal A activity also induced GL-3 reduction in skin, urine, and/or kidney. This is promising drug and is being studied in phase 3 studies.

Next:

Anticonvulsants

Class Summary

Antiseizure medications are the most helpful in alleviating the debilitating pain of neurologic involvement.

Phenytoin may act in the motor cortex where it may inhibit the spread of seizure activity. Activity of the brainstem centers responsible for the tonic phase of grand mal seizures also may be inhibited.

Individualize dosing; if the dose cannot be divided equally, the larger dose should be taken before retiring for the evening.

Agalsidase alfa is a recombinant form of the human enzyme alpha-galactosidase A, levels of which are deficient in persons with Fabry disease. Data from clinical trials show a decrease in GL-3 levels following enzyme replacement, reversal in lipid tissue storage, stabilized or improved renal and cardiac function, and reduced or relief from neuropathic pain. Following enzyme replacement, long-term use of neuropathic pain medication has been reduced.

Agalsidase beta (Fabrazyme) is manufactured by Genzyme Corporation (Cambridge, Mass) and is based on the expression of the human GLA gene in CHO cells.

Agalsidase alfa (Replagal) is manufactured by Transkaryotic Therapies (Cambridge, Mass) and is based on activation of the human GLA gene expression in human (skin) fibroblasts.

Previous

References

U.S. National Library of Medicine, part of the National Institutes of Health,. GLA. Genetics Home Reference. Available at http://ghr.nlm.nih.gov/gene=gla. Accessed: June 21, 2009.

Rosalie Elenitsas, MD Herman Beerman Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System